The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients

Hans Skovgaard Poulsen,1,2,* Thomas Urup,1,2,* Signe Regner Michaelsen,1,2 Mikkel Staberg,1,2 Mette Villingshøj,1,2 Ulrik Lassen1–3 1Department of Radiation Biology, 2Department of Oncology, 3Phase I Unit, The Finsencenter, Copenhagen University Hospital, Copenhagen, Denmark *These authors contributed equally to this work Abstract: Glioblastoma multiforme (GBM) remains one of the most devastating tumors, and patients have a median survival of 15 months despite aggressive local and systemic therapy, including maximal surgical resection, radiation therapy, and concomitant and adjuvant temozolomide. The purpose of antineoplastic treatment is therefore to prolong life, with a maintenance or improvement of quality of life. GBM is a highly vascular tumor and overexpresses the vascular endothelial growth factor A, which promotes angiogenesis. Preclinical data have suggested that anti-angiogenic treatment efficiently inhibits tumor growth. Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor A, and treatment has shown impressive response rates in recurrent GBM. In addition, it has been shown that response is correlated to prolonged survival and improved quality of life. Several investigations in newly diagnosed GBM patients have been performed during recent years to test the hypothesis that newly diagnosed GBM patients should be treated with standard multimodality treatment, in combination with bevacizumab, in order to prolong life and maintain or improve quality of life. The results of these studies along with relevant preclinical data will be described, and pitfalls in clinical and paraclinical endpoints will be discussed. Keywords: primary treatment, VEGF, quality of life, monoclonal antibody, patient survival, vascular tumor